Kainic acid 2-carboxy-3-carboxymethyl-4-isopropenylpyrrolidine

Description

(−)-(α)-Kainic acid is a cyclic analog of L-glutamate originally isolated from D. simplex that has neuroexcitatory activities. It binds to the homomeric kainate receptors GluK1, GluK2, GluK3, GluK4, and GluK5 (K_is = 75.9, 12.7, 32.8, 4.7, and 15 nM, respectively). (−)-(α)-Kainic acid (5 mM) induces calcium influx and membrane depolarization, as well as glutamate release, in rat brain synaptosomes. It induces chromatin condensation and nuclear membrane fragmentation, markers of apoptosis, in primary neonatal cerebellar granule neurons when used at a concentration of 100 μM. Intracerebroventricular administration of (−)-(α)-kainic acid induces convulsive behavior in rats (ED₅₀ = 0.51 nmol/animal) and induces seizures in mice with a 50% convulsive dose (CD₅₀) value of 0.39 nmol/animal. It has been commonly used to induce seizures in rodents.

Uses

Kainic acid is used to study mechanisms of excitation-induced apoptosis and epilepsy.

Uses

Kainic acid monohydrate has been used:

• As a convulsant to induce epileptogenesis and epilepsy in mice.
• To stimulate in vitro excitotoxic trauma in spiral ganglion neurons on inner hair cells.
• To induce seizures in rat model.
• To induce status epilepticus in adult male Wistar rats.

General Description

Kainic acid is an agonist for kainate-class ionotropic glutamate receptors. Kainate receptors directly gate ion channels and are generally excitatory. Excess stimulation by Kainic acid induces neurocytosis (apoptosis) and epileptic seizures.

Biochem/physiol Actions

Kainic acid monohydrate is an agonist at the kainate class of ionotropic glutamate receptors, which induces seizures and neurodegeneration in vivo and is used to induce experimental epilepsy in rodents and study the mechanisms of excitation-induced neuronal apoptosis.

in vivo

References

[1] NAREDLA KESAVA REDDY  Srivari C. Total Synthesis of ()-α-Kainic acid via Chirality Transfer through Ireland–Claisen Rearrangement[J]. The Journal of Organic Chemistry, 2013, 78 7: 3355-3360. DOI: 10.1021/jo400001t
[2] EMANUELLE SAGOT. Chemo-Enzymatic Synthesis of a Series of 2,4-Syn-Functionalized (S)-Glutamate Analogues: New Insight into the StructureActivity Relation of Ionotropic Glutamate Receptor Subtypes 5, 6, and 7[J]. Journal of Medicinal Chemistry, 2008, 51 14: 4093-4103. DOI: 10.1021/jm800092x
[3] ANNA PASTUSZKO  M. E  David F Wilson. Effects of Kainic Acid in Rat Brain Synaptosomes: The Involvement of Calcium[J]. Journal of Neurochemistry, 1984, 43 3: 747-754. DOI: 10.1111/j.1471-4159.1984.tb12796.x
[4] N.A SIMONIAN . Kainic acid induces apoptosis in neurons[J]. Neuroscience, 1996, 75 4: Pages 1047-1055. DOI: 10.1016/0306-4522(96)00326-0
[5] CHRISTIAN CHIAMULERA. Domoic Acid Toxicity in Rats and Mice after Intracerebroventricular Administration: Comparison with Excitatory Amino Acid Agonists[J]. Basic & Clinical Pharmacology & Toxicology, 1992, 70 2: 115-120. DOI: 10.1111/j.1600-0773.1992.tb00439.x
[6] QUN WANG. Kainic acid-mediated excitotoxicity as a model for neurodegeneration.[J]. Molecular Neurobiology, 2005, 31 1-3: 3-16. DOI: 10.1385/mn:31:1-3:003
[7] HELENA DOMIN . Neuroprotective potential of mGluR5 antagonist MTEP: effects on kainate-induced excitotoxicity in the rat hippocampus[J]. Pharmacological Reports, 2010, 62 6: Pages 1051-1061. DOI: 10.1016/s1734-1140(10)70367-4